DESCRIPTION (adapted from the Abstract): The underlying objective of the proposed research is to test the hypothesis that the antinociception of pregnancy and hormonally-simulated pregnancy (HSP) is mediated by a multiplicative interaction between spinal kappa and delta opioid systems and between these systems and descending noradrenergic pathways. The specific objectives are to (1) determine if the analgesia of pregnancy and HSP consists of the sum of separate, independent spinal cord analgesic systems or if it requires their concomitant activation; (2) determine if the antinociception of pregnancy and HSP is mediated in part by increased spinal kappa and delta receptor density and/or distribution; (3) determine if enhanced spinal noradrenergic tone is necessary for a substantial component of pregnancy analgesia and if this influence is mediated by the hypogastric nerve; and (4) determine if the newly-discovered spinal ORL1/nociceptin hypoanalgesic system modulates analgesia of pregnancy and HSP. All-in-all, this research should elucidate the component of the intrinsic pain-attenuating system that is activated during gestation and could provide a basis developing interventions for the management of pain in pregnancy and childbirth.